Cushing syndrome (CS), a fatal disease, is suspected in many thousands of patients each year, but confirmed in only a fraction of these. This project seeks to identify accurately which patients have Cushing syndrome, to define the etiology of their disease and to treat it optimally. A major goal during the past year was to better delineate, through the use of a validated survey instrument, the subjective quality of life of patients before and after treatment of Cushing syndrome. We want to delineate the subjective experience of hypercortisolism and the recovery period, and to evaluate whether patterns of response predict a later pattern of recovery. We use the entire SF-36 questionnaire developed by John Ware and colleagues, as a subset of the larger questionnaire administered in the Medical Outcomes Study. Since the SF-36 does not delineate areas related to social function, memory and cognition very well, we have added other questions in these domains taken from the Medical Outcomes Study. Patients also complete a symptom checklist and a questionnaire about recurrence, satisfaction with treatment, current treatment, and demographics. Initial analysis suggests that patients with active Cushing syndrome have great impairment in physical activities and cognitive function and that they also limit social activities. There are also significant, but less profound abnormalities in the sense of well-being and general health perception and activities because of emotional problems are increased compared to the general population. Preliminary evaluation of patients after treatment suggests improvement in these areas, but some patients do not regain scores similar to the general population as long as two years after treatment, suggesting significant long-term impairment of quality of life in some individuals with Cushing syndrome. Another evaluation was directed to the need for parenteral medical therapy of hypercortisolism to inhibit steroidogenesis and reduce the risk of complications. We used the propylene glycol preparation of etomidate available in the United States to control hypercortisolism in a 39-year-old man with ectopic ACTH secretion who was unable to take oral medications. Etomidate was administered over a period of 5 1/2 months. We titrated the dose of etomidate daily using serum cortisol levels, to avoid steroid over replacement and allow for a response to ongoing stress. A reduced dose during a period of acute renal failure achieved adequate control of hypercortisolemia. Suppression of steroidogenesis persisted for at least 14 days and perhaps as long as 6 weeks after cessation of the medication. Except for transient myoclonus, the patient tolerated this preparation well. This demonstrated that parenteral propylene glycol containing etomidate can be used safely for a prolonged period to reduce hypercortisolemia in patients unable to take oral medications.